Skip to main content
SpringerLink
Log in

Quantitation of somatostatin receptor type 2 in neuroendocrine (merkel cell) carcinoma of the skin by competitive RT-PCR

  • Clinical Research
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Merkel cell neuroendocrine carcinoma (MCC) is a rare but highly aggressive small-cell tumor affecting the skin and, rarely, the lymph nodes (in the absence of a primary site). MCC expresses several neuroendocrine markers, but no data are available on the presence of somatostatin receptors (SSTR) in this tumor. SSTR type 2, mostly detected in normal and neoplastic nervous and neuroendocrine cells, bind the somatostatin analog octreotide with the highest affinity. The aim of this study was to investigate the presence of SSTR2 mRNA in MCC, to quantitate their occurrence in individual tumors, and to correlate the presence of SSTR2s with tumor progression and outcome. SSTR2 mRNA was present in 9/10 cases of primary or metastatic MCC by reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot. A variable amount of receptors was found, spanning at least two log units (106–108 mol/μg RNA). Presence of SSTR2 was not correlated with clinical parameters or evolution. It is concluded that MCC shares the property of other neuroendocrine tumors of expressing SSTR2; in a subset of MCC, endowed with high amounts of SSTR2 Octreotide may be an adjunct in the therapeutic strategy for these tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Toker C. Trabecular carcinoma of the skin. Arch Dermatol 105:107–110, 1972.

    Article  PubMed  CAS  Google Scholar 

  2. Foschini MP, Eusebi V. The spectrum of endocrine tumors of skin. Curr Diagn Pathol 2:2–9, 1995.

    Article  Google Scholar 

  3. Gould VE, Moll R, Moll I, Lee I, Franke WW. Biology of disease. Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest 52:334–353, 1985.

    PubMed  CAS  Google Scholar 

  4. Pilotti S, Rilke F, Lombardi L. Neuroendocrine (Merkel cell) carcinoma of the skin. Am J Surg Pathol 6:243–254, 1982.

    PubMed  CAS  Google Scholar 

  5. Rosen ST, Gould VE, Salwen HR, Herst CV, Le Beau MM, Lee I, et al. Establishment and characterization of a neuroendocrine skin carcinoma cell line. Lab Invest 56:302–312, 1987.

    PubMed  CAS  Google Scholar 

  6. Sibley RK, Dehner LP, Rosai J. Primary neuroendocrine (Merkel cell?) carcinoma of the skin. I. A clinicopathologic and ultrastructural study of 43 cases. Am J Surg Pathol 9:95–108, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. Wick MR, Kaye VN, Sibley RK, Tyler R, Frizzera G. Primary neuroendocrine carcinoma and small-cell malignant lymphoma of the skin. A discriminant immunohistochemical comparison. J Cutan Pathol 13:347–358, 1986.

    Article  PubMed  CAS  Google Scholar 

  8. Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. Mod Pathol 8:384–388, 1995.

    PubMed  CAS  Google Scholar 

  9. Moll R, Osborne M, Hartschuh W, Moll I, Mahrle G, Weber K. Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas (Merkel cell tumors): immunocytochemical and biochemical analysis of twelve cases. Ultrastruct Pathol 10:473–495, 1986.

    PubMed  CAS  Google Scholar 

  10. Shah IA, Netto D, Schlageter MO, Muth C, Fox I, Manne RK. Neurofilaments immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma. Mod Pathol 6:3–9, 1993.

    PubMed  CAS  Google Scholar 

  11. Eusebi V, Capella C, Cossu A, Rosai J. Neuroendocrine carcinoma within lymph nodes in the absence of a primary tumor, with special reference to merkel cell carcinoma. Am J Surg Pathol 16:658–666, 1992.

    Article  PubMed  CAS  Google Scholar 

  12. Haag ML, Glass LF, Fenske NA. Merkel cell carcinoma. Diagnosis and treatment. Dermatol Surg 21:669–683, 1995.

    Article  PubMed  CAS  Google Scholar 

  13. O’Connor WJ, Brodland DG. Merkel cell carcinoma. Dermatol Surg 22:262–267, 1996.

    Article  PubMed  CAS  Google Scholar 

  14. Cockerell CJ, Mack Sexton F. Evaluation of small-cell neoplasms of the skin. Clin Dermatol 9:227–233, 1991.

    Article  PubMed  CAS  Google Scholar 

  15. Wilder RB, Harari PM, Graham AR, Shimm DS, Cassady JR. Merkel cell carcinoma. Improved locoregional control with postoperative radiation therapy.Cancer 68:1004–1008, 1991.

    Article  PubMed  CAS  Google Scholar 

  16. Wynne CJ, Kearsley JH. Merkel cell tumor. A chemosensitive skin cancer. Cancer 62:28–33, 1988.

    Article  PubMed  CAS  Google Scholar 

  17. Patel YC, Murthy KK, Escher EE, Banville D, Spiess J, Srikant CB. Mechanism of action of somatostatin: an overview of receptor function and studies of the molecular characterization and purification of somatostatin receptor proteins. Metabolism 39:63–69, 1990.

    Article  PubMed  CAS  Google Scholar 

  18. Reubi JC, Schaer JC, Waser B, Mengod G. Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors usingin situ hybridization. Cancer Res 54:3455–3459, 1994.

    PubMed  CAS  Google Scholar 

  19. Yamada Y, Post SR, Wang K, Tager HS, Bell GI, Seino S. Cloning and functional characterisation of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract and kidney. Proc Natl Acad Sci USA 89:251–255, 1992.

    Article  PubMed  CAS  Google Scholar 

  20. Raulf F, Perez J, Hoyer D, Bruns C. Differential expression of five somatostatin receptor subtypes, SSTR1-5, in the CNS and peripheral tissue. Digestion 55:46–53, 1994.

    PubMed  CAS  Google Scholar 

  21. Buscail L, Delesque N, Esteve JP, Saint-Laurent N, Prats H, Clerc P, et al. Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptors subtypes SSTR1 and SSTR2. Proc Natl Acad Sci USA 91:2315–2319, 1994.

    Article  PubMed  CAS  Google Scholar 

  22. Buscail L, Esteve JP, Saint-Laurent N, Bertrand V, Reisine T, O’Carrol AM, et al. Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by SSTR2 and SSTR5 somatostatin receptors through different mechanisms. Proc Natl Acad Sci USA 92:1580–1584, 1995.

    Article  PubMed  CAS  Google Scholar 

  23. Di Bartolomeo M, Bajetta E, Buzzoni R, Mariani L, Carnaghi C, Somma L, et al. Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. Cancer 77:402–408, 1996.

    Article  PubMed  Google Scholar 

  24. Kubota A, Yamada Y, Kagimoto S, Shimatsu A, Imamura M, Tsuda K, et al. Identification of somatostatin analogue SMS 201–995 in treatment of human endocrine tumors. J Clin Invest 93:1321–1325, 1994.

    Article  PubMed  CAS  Google Scholar 

  25. Lamberts SWJ, Hofland LJ, van Koetsveld PM, Reubi JC, Bruining HA, Bakker WH, et al. Parallelin vivo andin vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: consequences with regard to diagnosis, localization, and therapy. J Clin Endocrinol Metab 71:566–574, 1990.

    Article  PubMed  CAS  Google Scholar 

  26. Lamberts SWJ, Krenning EP, Reubi JC. The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr Rev 12:450–482, 1991.

    Article  PubMed  CAS  Google Scholar 

  27. Maggi M, Baldi E, Finetti G, Franceschelli F, Brocchi A, Lanzillotti R, et al. Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines. Cancer Res 54:124–133, 1994.

    PubMed  CAS  Google Scholar 

  28. Sestini R, Orlando C, Peri A, Tricarico C, Pazzagli M, Serio M, et al. Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction. Clin Cancer Res 2:1757–1765, 1996.

    PubMed  CAS  Google Scholar 

  29. Viollet C, Faivre-Bauman A, Zhang J, Llorens-Cortes C, Loudes C, Kordon C, et al. Differential expression of somatostatin receptors by quantitative PCR in the rat brain. Comptes Rendus Acad Sci 318:851–857, 1995.

    CAS  Google Scholar 

  30. Hsu SM, Raine M, Fanger H. Use of avidineperoxidase complex (ABC) in immunoperoxidase technique: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29:577–580, 1981.

    PubMed  CAS  Google Scholar 

  31. Chirgwin JM, Przybyla AE, Mac Donald RJ, Rutter WJ. Isolation of biologically active RNA from sources enriched in ribonuclease. Biochemistry 18:5294–5297, 1979.

    Article  PubMed  CAS  Google Scholar 

  32. Pagani A, Forni M, Tonini GP, Papotti M, Bussolati G. Expression of members of the chromogranin family in primary neuroblastomas. Diagn Mol Pathol 1:16–24, 1992.

    Article  PubMed  CAS  Google Scholar 

  33. Gerdes HH, Rosa P, Phillips E, Baeuerle PA, Frank R, Argps P, et al. The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH-and Calcium-induced aggregation. J Biol Chem 264:12,009–12,015, 1989.

    CAS  Google Scholar 

  34. Gussow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, et al. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J Immunol 139:3132–3138, 1987.

    PubMed  CAS  Google Scholar 

  35. Helman IJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, et al. Molecular cloning and primary structure of human chromogranin A (Secretory protein I) cDNA. J Biol Chem 263:11,559–11,563, 1988.

    CAS  Google Scholar 

  36. Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 339:237–238, 1989.

    Article  PubMed  CAS  Google Scholar 

  37. Brinkschmidt C, Stolze P, Fahrenkamp AG, Hundeiker M, Fisher-Colbrie R, Zelger B, et al. Immunohistochemical demonstration of chromogranin A, chromogranin B, and secretoneurin in Merkel cell carcinoma of the skin. Appl Immunohistochem 3:37–44, 1995.

    Google Scholar 

  38. Sibley RK, Dehner LP, Rosai J. Primary neuroendocrine (Merkel cell?) carcinoma of the skin. II. An immunocytochemical study of 21 cases. Am J Surg Pathol 9:109–116, 1985.

    Article  PubMed  CAS  Google Scholar 

  39. Papotti M, Macri L, Bussolati G, Reubi JC. Correlative study on neuroendocrine differentiation and presence of somatostatin receptors in breast carcinomas. Int J Cancer 43:365–369, 1989.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences and Oncology, University of Turin, Via Santena 7, I-10126, Torino, Italy

    Mauro Papotti MD, Luigia Macri’ MD, Alberto Pagani MD & Gianni Bussolati MD, Frcpath

  2. Department of Dermatology, University of Turin, Via Santena 7, I-10126, Torino, Italy

    Filippo Aloi MD

Authors
  1. Mauro Papotti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luigia Macri’ MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alberto Pagani MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filippo Aloi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gianni Bussolati MD, Frcpath
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Papotti, M., Macri’, L., Pagani, A. et al. Quantitation of somatostatin receptor type 2 in neuroendocrine (merkel cell) carcinoma of the skin by competitive RT-PCR. Endocr Pathol 10, 37–46 (1999). https://doi.org/10.1007/BF02738814

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02738814

Key words

Search

Navigation